Fulvestrant formulations and methods of their use

Abstract

The disclosure is directed to fulvestrant formulations including suspensions of fulvestrant particles suitable for injection. The formulations can comprise fulvestrant particles having an LD Dv(10) less than about 3 microns, for example, between about 1 micron to about 3 microns, an LD Dv(50) less than about 35 microns, for example, between about 2 microns and about 35 microns, and an LD Dv(90) less than about 120 microns, for example, between about 4 microns and about 120 microns. The formulations can comprise fulvestrant particles having a CE Dv(90) less than about 200 microns, for example, between about 10 microns and about 200 microns, a CE Dv(50) less than about 60 microns, for example, between about 5 microns and about 60 microns, and a CE Dv(10) less than about 25 microns, for example, between about 1 microns and about 25 microns.

What is claimed is: 
     
       1. A method of forming an aqueous fulvestrant suspension comprising:
 mixing an aqueous medium and at least one stabilizer to form a suspension vehicle, the at least one stabilizer comprising:
 a surfactant and 
 a polyvinylpyrrolidone, polyethylene glycol with an average molecular weight of about 3350 g/mol, a carboxymethylcellulose sodium, a non-electrolyte, or a combination thereof; 
 
 adding an amount of fulvestrant to the suspension vehicle; and 
 dispersing the fulvestrant in the suspension vehicle to form an aqueous fulvestrant suspension; 
 wherein the aqueous fulvestrant suspension comprises fulvestrant particles having one or more of:
 a laser diffraction determined (LD) Dv(10) from about 1 micron to about 3 microns; 
 an LD Dv(50) from about 2 microns to about 35 microns; and 
 an LD Dv(90) from about 4 microns to about 120 microns; 
 
 and having one or more of:
 a microscopy image capture determined (CE) Dv(90) from about 10 microns and about 200 microns; 
 a CE Dv(50) from about 5 microns to about 60 microns; and 
 CE Dv(10) from about 1 microns to about 25 microns. 
 
 
     
     
       2. The method of  claim 1 , further comprising high pressure homogenizing the aqueous fulvestrant suspension. 
     
     
       3. The method of  claim 2 , wherein the high pressure homogenization is performed at a pressure of about 15,000 psi to about 45,000 psi. 
     
     
       4. The method of  claim 2 , further comprising adding an electrolyte to the homogenized aqueous fulvestrant suspension and mixing the electrolyte into the suspension. 
     
     
       5. The method of  claim 2 , further comprising adding another non-electrolyte to the homogenized aqueous fulvestrant suspension and mixing the other non-electrolyte into the suspension.